Prostaglandins in Cancer Cell Adhesion, Migration, and Invasion
Figure 6
Linking PGE2 to adhesion, migration, and invasion. Prostaglandin E2 elicits profound changes in tumor cells that result in the disassociation of cadherin-mediated cell connections. This is accompanied by the establishment/turnover of integrin-mediated interactions with extracellular matrix during adhesion and subsequent migration and invasion. Stimulation of EP2 or 4 receptors leads to the activation of adenylate cyclase and results in the production of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). The accumulation of cAMP in the cell cytoplasm activates protein kinase A (PKA) and the phosphorylation of downstream targets. This accumulation of cAMP can also activate exchange protein activated by cAMP (Epac). The activation of Epac may involve the interactions with Rap1 and subsequent downstream signals that influence adhesion, migration, and invasion. The activation of EP1 and EP3 leads to Ca2+ influx and the activation of Rho-mediated signal transduction that influences cadherin function during the disassociation of cadherin-based adhesive contacts or integrin interactions with the extracellular matrix contacts.
